Management of Obesity as an Endocrine Disease

W. Timothy Garvey, MD, examined the role of endocrine systems in the pathophysiology of obesity and discussed how weight loss can impact endocrine and metabolic abnormalities involved in the disease process at the American Association of Clinical Endocrinologists (AACE) 25th Annual Scientific & Clinical Congress, May 25-29, 2016 in Orlando, Florida.

Dr. Garvey is Professor and Chair of the Department of Nutrition Sciences at the University of Alabama at Birmingham. He also is Director of the UAB Diabetes Research Center and GRECC Investigator and Staff Physician at the Birmingham VA Medical Center.

Role of the Enteroendocrine-Hypothalamic Axis in Obesity
"The enteroendocrine-hypothylamic axis plays a role in obesity not only in promoting excess adiposity and a positive energy balance, but also in protecting against excess adiposity in the face of weight loss interventions," Dr. Garvey said.

Tissues in peripheral organs, primarily in the intestines, release hormones into the bloodstream that signal the hypothalamus to regulate food intake. In obesity, appetite-suppressing anorexigenic hormones (leptin, peptide YY, cholecystokinin, glucagon-like peptide-1, amylin, and insulin) are decreased and orexigenic hormones (ghrelin) are increased.

"In the disease of obesity, these hormone/target-cell interactions are dysregulated and generate a higher degree of adiposity; this dysregulation also plays a role in protecting against weight loss and promoting weight regain in the face of the weight loss intervention," Dr. Garvey explained.

Dr. Garvey then explained the impact of weight loss on endocrinopathies by using adipose tissue dysfunction and polycystic ovary syndrome (PCOS) as examples.

Adipose Tissue Dysfunction and Cardiometabolic Disease
"I believe there is a single underlying pathophysiological process that is part of this disease progression to both metabolic and vascular disease in patients with insulin resistance and obesity," said Dr. Garvey. One example of this involves the decrease in adiponectin secretion by fat cells, he said.

Dr. Garvey summed up current knowledge on this topic by explaining that as environment and genetics interact to increase energy intake and decrease energy expenditure, fat storage increases. If this occurs in an insulin-sensitive background, biomechanical complications of obesity (eg, osteoarthritis, sleep apnea, urinary incontinence) may occur.3 However, in an insulin-resistant environment, excess fat storage causes inflammation in fat and predisposes patients to the cardiometabolic nexus of diseases all emanating from adipocyte dysfunction (eg, cardiovascular disease, diabetes, hypertension, nonalcoholic fatty liver disease, metabolic syndrome, and prediabetes).3

Infertility in PCOS
PCOS is linked to a number of metabolic and reproductive issues, with increasing BMI being linked to worse manifestations of PCOS, Dr. Garvey explained. While only approximately 50% of patients with PCOS are obese, all are insulin resistant, he said.

A number of different treatments are available for individual manifestations of PCOS, such as clomiphene for anovulation, oral contraceptive pills for acne, or metformin for insulin resistance. However, weight loss addresses all the manifestations of PCOS, he said.4

In a 2015 study by Legro et al, a preconception weight loss intervention used before standardized ovulation induction with clomiphene citrate markedly increased the probability of life births compared with oral contraception pretreatment.5

Other research has linked reductions in intraabdominal fat to increased fertility in women with PCOS who are obese.6 In addition, a study by Kort et al suggests that a greater than 10% reduction in body weight is needed to increase the rate of conception and live birth rate in overweight patients with infertility.7

Dr. Garvey summarized that, "a 5% to 10% weight loss can improve the metabolic syndrome traits in PCOS, but a greater than 10% weight loss is needed to treat infertility, anovulation, or dysmenorrhea. If a patient is using weight-loss medications, of course, you should discontinue the medications before attempts at conception are made."

Dr. Garvey concluded that "endocrinopathy can be involved both in the pathophysiology of obesity and underlie the therapeutic responses with weight loss." This understanding can be translated into a complications-centric approach to treatment, in which increased intensity of therapy is used for patients with more severe complications, to achieve the best outcomes with an optimal benefit/risk ratio, he added.